Rad52 deficiency decreases development of lung squamous cell carcinomas by enhancing immuno-surveillance. Oncotarget 2017 May 23;8(21):34032-34044
Date
04/19/2017Pubmed ID
28415565Pubmed Central ID
PMC5470949DOI
10.18632/oncotarget.16371Scopus ID
2-s2.0-85019953428 (requires institutional sign-in at Scopus site) 8 CitationsAbstract
RAD52 is involved in homologous recombination and DNA repair. This study focuses on lung cancer progression and how the DNA repair gene, Rad52, enables tumor cells to have sufficient genome integrity, i.e., the ability to repair lethal DNA damage, to avoid cell death. In this report, we analyze the phenotypic differences between wild type and Rad52-/- in inhibition of tumor phenotypes including cell growth, viability, cytolysis, and immune profiling. We demonstrated that loss of Rad52 not only increases the death of cells undergoing carcinogen-induced transformation in vivo, but that Rad52 loss also augments in vivo antitumor activity through an enhanced capacity for direct killing of LLC tumor cells by stimulated Rad52-/- NK and CD8+ T cells. We hypothesize that upon DNA damage, wild type cells attempt to repair DNA lesions, but those cells that survive will continue to divide with damage and a high likelihood of progressing to malignancy. Loss of Rad52, however, appears to increase genomic instability beyond a manageable threshold, acceding the damaged cells to death before they are able to become tumor cells. Our results suggest a key role for the complex interplay between the DNA damage response and host immunity in determining risk for Squamous Cell Lung Carcinoma.
Author List
Lieberman R, Pan J, Zhang Q, You MMESH terms used to index this publication - Major topics in bold
AnimalsCD8-Positive T-Lymphocytes
Carcinoma, Lewis Lung
Carcinoma, Squamous Cell
Cell Proliferation
Cell Survival
DNA Damage
Disease Progression
Gene Knockout Techniques
Humans
Immunologic Surveillance
Killer Cells, Natural
Mice
Rad52 DNA Repair and Recombination Protein
